Zhengshan Chen

Lili Wang, M.D., Ph.D.

  • Associate Professor, Department of Systems Biology

Lili Wang, M.D., Ph.D.

Research Focus :
  • Genetic alterations and CLL biology
  • RNA splicing dysregulation and oncogenesis
Lili Wang, M.D., Ph.D., has joined City of Hope as an associate professor in the Department of Systems Biology. She comes to City of Hope from Harvard Medical School in Boston, where she was an instructor in the Department of Medical Oncology at Dana-Farber Cancer Institute.
 
Dr. Wang received her Ph.D. in immunology from Tokai University in Japan under mentorship of Dr. Sonoko Habu. She continued her scientific training at the University of Illinois at Chicago in Amy Kenter’s laboratory, and at Dana-Farber Cancer Institute in the laboratory of Catherine Wu, M.D. Her research focuses on the genetics of chronic lymphocytic leukemia.
 
Dr. Wang published landmark papers in prestigious journals including New England Journal of Medicine and Cancer Cell. She is the recipient of several awards and has recently received her first R01 grant from the National Cancer Institute to study mouse models of B cell CLL with a focus on the splicing factor SF3B1. She is frequently invited to present her work at national and international conferences and holds several memberships in professional societies including the American Society of Hematology and American Society of Cancer Research.
 
In the Department of Systems Biology, she will expand her research program to systematically study RNA splicing dysregulation and oncogenesis.
  • 2017-present, Associate Professor, Department of Systems Biology, Beckman Research Institute of City of Hope, Duarte, CA
  • 2013-2017, Instructor, Division of Hematologic Neoplasia, Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA

Degrees

  • 2003, Ph.D., Immunology, Tokai University
  • 1998, MS, Immunology, China Medical University
  • 1994, M.D., China Medical University

Fellowship

  • 2003-2008, Department of Microbiology and Immunology, University of Illinois at Chicago, Chicago, IL
  • 2008-2013, Division of Hematologic Neoplasia, Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA
Dr. Wang’s laboratory focuses on a clinically heterogeneous blood disease, chronic lymphocytic leukemia (CLL), the most common form of adult leukemia in North America. In the past few years, worldwide efforts using next-generation sequencing (NGS) technology have identified numerous cancer driving genetic events across various cancer types including CLL. How these somatic events drive disease initiation, progression, and relapse has become a central question in the field of cancer research. The Wang laboratory will systematically dissect somatic mutations contributing to the disease phenotype utilizing CRISPR/Cas9 technology and single-cell sequencing which will be coupled with murine models as well as human CLL samples. The ultimate goal will be to discover novel prognosis markers and design better therapeutic approaches for this heterogeneous disease.
 
Recently, Dr. Wang has leveraged comprehensive integrated approaches including NGS and RNA-sequencing of primary patient samples to understand how RNA splicing factor mutations of the gene SF3B1 impact CLL biology. This gene is found to be frequently mutated and associated with poor clinical outcome in CLL.  Moreover, mutations in this gene were also discovered in myelodysplasia, uveal melanoma, breast and pancreatic cancer, raising the question of how altered RNA splicing events are linked to oncogenesis. At City of Hope, Dr. Wang’s group will delineate how these splicing mutations lead to the progression and relapse of CLL as well as how RNA splicing dysregulation contributes to leukemogenesis.
 
Dr. Wang obtained her M.D. at the China Medical University (Shenyang, China) and her Ph.D. degree at the Tokai University (Isehara, Japan). She received her postdoctoral training at the University of Illinois   (Chicago, IL) and Dana-Farber Cancer Institute/Harvard Medical School (Boston, MA). In 2017, Dr. Wang joined the Department of Systems Biology at the Beckman Research Institute. She is also a member of the Toni Stephenson Lymphoma Center at City of Hope.
 
  • Senoo M, Mochida N, Wang L, Shinkai Y, Habu, S. Limited effect of chromatin remodeling on Db-to-Jb in CD4CD8 thymocyte: implications for a new aspect in the regulation of TCRb recombination. Int. Immunol. 2001 13: 1405-1414.
  • Wang L, Senoo M, Habu S. Differential regulation between gene expression and histone H3 acetylation in the variable regions of the TCRb locus. Biochem Biophys Res Comm. 2002 298: 420-426.
  • Senoo M, Wang L, Suzuki D, Takeda N, Shinkai Y, Habu, S. Increase of TCRVb accessibility within Eb regulatory region influences its recombination frequency but not allelic exclusion. J. Immunol. 2003 171:829-35.
  • Wang L, Kametani Y, Habu S. T cell specific enhancement of histone H3 acetylation in 5' flanking region of the IL-2 gene. Biochem Biophys Res Comm. 2005 331: 589-94.
  • Suzuki D, Wang L, Senoo M, Habu S. The positional effect of Eb on Vb genes of TCRb chain in the ordered rearrangement and allelic exclusion. Int Immunol. 2005 17(12): 1553-60.
  • Wang L, Whang N, Wufferel R, Kenter AL. AID dependent histone acetylation is associated with class switch recombination. J Exp Med. 2006 203:215-26.
  • Wang L, Wufferel R, Kenter AL. NF-kB binds to the Immunoglobulin Sg3 and Sg1 regions in vivo during class switch recombination. Eur J Immuol. 2006 36: 3315-23.
  • Wuerffel, R., Wang, L. Grigera, F. Manis, J. Selsing, E, Perlot, T. Alt, FW. Cogne, M. Pinaud E and Kenter, A. S-S synapsis during class switch recombination is promoted by distantly located transcriptional elements and activation-induced deaminase. Immunity. 2007 27(5): 711-22.
  • Shen HM, Bozek G, Pinkert CA, McBride K, Wang L, Kenter AL, Storb U. Expression of AID transgene is regulated in activated B cells but not in resting B cells and kidney. Mol Immunol. 2008 45(7): 1883-92.
  • Kametani Y, Wang L, Koduka K, Sato T, Katano I, Habu S. Rapid histone deacetylation and transient HDAC association in the IL-2 promoter region of TSST-1-stimulated T cells. Immunol Lett. 2008 119(1-2): 97-102.
  • Wang L, Wuerffel R, Feldman S. Khamlichi A, Kenter, AL. S Region Sequence, RNA Polymerase II and Histone modifications create chromatin accessibility during class switch recombination. J Exp Med. 2009 106(8): 1817-30.
  • Davids MS, Deng J, Wiestner A, Lannutti BJ, Wang L, Wu CJ, Wilson WH, Brown JR, Letai A. Decreased mitochondrial apoptotic priming underlies stromal-mediated treatment resistance in chronic lymphocytic leukemia. Blood. 2012 120(17): 3501-9.
  • Wang L, Lawrence MS, Wan Y, Stojanov P, Sougnez C, Stevenson K, Werner L, Sivachenko A, Deluca DS, Zhang L, Zhang W, Vartanov AR, Fernandes SM, Goldstein NR, Folco EG, Cibulskis K, Tesar B, Sievers QL, Shefler E, Gabriel S, Hacohen N, Reed R, Meyerson M, Golub TR, Lander ES, Neuberg D, Brown JR, Getz G, Wu CJ. SF3B1 and other novel cancer genes in chronic lymphocytic leukemia. N Engl J Med. 2011 365(26): 2497-506.
  • Shalek AK, Gaublomme JT, Wang L, Yosef N, Hacohen N, Neuberg D, Regev A, Wu CJ, Park H. Sensitivity to Wnt pathway inhibition in CLL is associated with specific gene signature. Nano Lett. 2012, 12: 6498-6504.
  • Landau DA, Carter SL, Stojanov P, McKenna A, Stevenson K. Lawrence MS, Cougnez C, Stewart C, Sivachenko A, Wang L, Wan Y, Zhang W, Shukla SA, Vartanov A, Fernandes SM, Saksena G, Cibulskis K, Tesar B, Babriel S, Hacohen N, meyerson M, Lander ES, Neuberg D, Brown JR, Getz G, Wu CJ. Evolution and impact of subclonal mutations in chronic lymphocytic leukemia. Cell. 2013 152 (4): 714-26.
  • Landau DA, Clement K, Ziller MJ, Boyle P, Fan J, Gu H, Stevenson K, Sougnez C, Wang L, Li S, Kotlizr D, Zhang W, Ghandi M, Garraway L, Fernandes SM, Livak KJ, Gabriel S, Gnirke A, Lander ES, Brown JR, Neuberg D, Kharchenko PV, Hacohen N, Getz G, Eissner A, Wu CJ. Locally disordered methylation forms the basis of intratumor methylome variation in chronic lymphocytic leukemia. Cancer Cell. 2014 26(6): 815-25.
  • Wang L, Shalek AK, Lawrence MS, Gaublomme JT, Pochet N, Stojanov P, Sougnez C, Stevenson K, Neuberg D, Cibulskis K, Zhang W, Sievers QL, Vartanov AR, Goldstein NR, Sutton A, Van de Peer Y, Gabriel S, He X, Lander ES, Hacohen N, Regev A, Getz G, Brown JR, Park H, Wu CJ. Somatic mutation as a mechanism of Wnt/-catenin pathway activation in CLL. Blood. 2014 124(7): 1089-98.
  • Burger JA, Landau DA, Taylor-Weiner A, Bozic I, Zhang H, Sarosiek K, Wang L, Stewart C, Fan J, Hoellenriegel J, Sivina M, Dubuc AM, Fraser C, Han Y, Li S, Livak KJ, Zou L, Wan Y, Konoplev S, Sougnez C, Brown JR, Abruzzo LV, Carter SL, Keating MJ, Davids MS, Wierda WG, Cibulskis K, Zenz T, Werner L, Dal Cin P, Kharchencko P, Neuberg D, Kantarjian H, Lander E, Gabriel S, O'Brien S, Letai A, Weitz DA, Nowak MA, Getz G, Wu CJ. Clonal evolution in patients with chromic lymphocytic leukemia developing resistance to BTK inhibition. Nat Commun. 2016 7:11589.
  • Obeng EA, Chappell RJ, Seiler M, Chen MC, Campagna DR, Schmidt PJ, Schneider RK, Lord AM, Wang L, Gambe RG, McConkey ME, Ali AM, Raza A, Yu L, Buonamici S, Smith PG, Mullally A, Wu CJ, Fleming MD, Ebert BL. Physiologic Expression of Sf3b1(K700E) Causes Impaired erythropoiesis, aberrant Splicing, and sensitivity to therapeutic spliceosome modulation. Cancer Cell. 2016 30(3): 404-17.
  • Wang L, Brooks AL, Fan J, Wan Y, Gambe R, Li S, Hergert S, Freeman SS, Levin JZ, Fan L, Seiler M, Buonamici S, Smith PG, Chau KF, Cibulskis CL, Zhang W, Rassent LZ, Ghia EM, Kipps TJ, Fernandes S, Bloch DB, Kotliar D, Landau DA, Shukla S, Aster JC, Reed R, DeLuca DS, Brown JR, Neuberg D, Getz G, Livak KJ, Meyerson MM, Kharchenko PV, Wu CJ. Transcriptomic characterization of SF3B1 mutation reveals its pleiotropic effects in chronic lymphocytic leukemia. Cancer Cell. 2016 30(5): 750-763.
  • Feldman S, Wuerffel R, Achour I, Wang L, Carpenter PB, Kenter AL. 53BP1 contributes to Igh locus chromatin topology during class switch recombination. J Immunol. 2017 198(6); 2434-2444.
  • Wang L, Fan J, Francis J, Zhang C, Herger S, Gambe R, Li S, Zhou C, Yang C, Xiao S, Dal Cin P, Bowden M, Kotliar D, Shukla S, Brown JR, Neuberg D, Livak KJ, Kharchenko PV, Wu CJ. Integrated single-cell genetic and transcriptional analysis suggests novel drivers of chronic lymphocytic leukemia. Genome Res (in print). 2017.
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